Process for preparing antibiotics MA 144-M1 and MA 144-M2

Abstract

New antitumor agents designated MA 144-M1 and MA 144-M2, which are anthracycyline glycosides and inhibit the growth of gram-positive bacteria, e.g. Staphyococcus aureus, Bacillus subtilis and Sarcina lutea, and inhibit the growth of animal tumors such as leukemia L 1210, P 388 and sarcoma 180 are produced by fermentation of MA 144-producing strains of streptomyces and by the chemical or enzymatic conversion of aclacinomycin A or cinerubin A.

We claim: 
     
       1. The process for producing the anthracycline glycoside MA 144-M 1  which comprises culturing a MA 144-M 1  -producing strain belonging to the genus Streptomyces under submerged aerobic conditions in a nutrient medium containing a carbon source and a nitrogenous nutrient until a substantial amount of MA 144-M 1  is produced by said organism in said nutrient medium and recovering the MA 144-M 1  from the nutrient medium substantially free of substances co-produced therewith. 
     
     
       2. The process of claim 1 in which a MA 144-M 1  -producing strain selected from the group consisting of Streptomyces galilaeus MA 144-M 1  ATCC 31133 (FERM P-2455), Streptomyces sp. ME 505-HE1 ATCC 31273 (FERM P-3667), S. galilaeus ATCC 14969, S. cinereoruber ATCC 19740, S. niveoruber ATCC 14971, S. antibioticus ATCC 8663, S. purpurascens ATCC 25489 and mutants thereof is cultured in a nutrient medium at a temperature in the range of 20° C. to 35° C. 
     
     
       3. The process of claim 1 in which the MA 144-M 1  produced in the culture broth is extracted and purified by a process which includes at least one process selected from the group consisting of solvent extraction, solvent precipitation, concentration, counter-current distribution, chelation with metal ions, adsorption to the adsorbent, and adsorption followed by elution from an ion exchange resin, an adsorbent siliceous earth or a synthetic adsorbent. 
     
     
       4. The process for producing the anthracycline glycoside MA 144-M 2  which comprises culturing a MA 144-M 2  -producing strain belonging to the genus Streptomyces under submerged aerobic conditions in a nutrient medium containing a carbon source and a nitrogenous nutrient until a substantial amount of MA 144-M 2  is produced by said organism in said nutrient medium and recovering the MA 144-M 2  from the nutrient medium substantially free of substances co-produced therewith. 
     
     
       5. The process of claim 4 in which a MA 144-M 2  -producing strain selected from the group consisting of Streptomyces galilaeus MA 144-M 1  ATCC 31133 (FERM P-2455), Streptomyces sp. ME 505 HE1 ATCC 31273 (FERM P-3667), S. galilaeus ATCC 14969, S. cinereoruber ATCC 19740, S. niveoruber ATCC 14971, S. antibioticus ATCC 8663, S. purpurascens ATCC 25489 and mutants thereof is cultured in a nutrient medium at a temperature in the range of 20° C. to 35° C. 
     
     
       6. The process of claim 4 in which the MA 144-M 2  produced in the cultured broth is extracted and purified by a process which includes at least one process selected from the group consisting of solvent extraction, solvent precipitation, concentration, counter-current distribution, chelation with metal ions, adsorption to the adsorbent, and adsorption followed by elution from an ion exchange resin, an adsorbent siliceous earth or a synthetic adsorbent.